The aims of this project are to identify the molecular origins of the similarities in the affinities and kinetics of interaction of effectors for the two related proteins, acetylcholinesterase and acetylcholine receptor. The molecular details by which ligands interact with these proteins and the effect of such interactions on the conformation of the protein are primary goals of the proposed research. Towards these goals we plan to investigate: (a) the role of chemical bonding, as indicated by the formation of acylenzyme intermediates and the formation of spectrophotometrically detectable transition-state analog complexes; (b) the nature of the protein environment, as indicated by conformational changes induced by ligand-binding to active sites and to peripheral sites, and (c) the molecular nature of the structural changes, as interpreted from a variety of signals of ligand and protein structure. A longer range goal is to relate the structural and chemical bonding changes to the mechanism of fucntion of the acetylcholine receptor in situ; that is, its physiological role in regulating the flow of ions across the cell membrane in response to cholinergic effectors.